CDC: Adenovirus should be considered in diagnosis of acute hepatitis in children
Several cases of acute, severe hepatitis in children in Alabama provided additional evidence in support of a possible link between this illness and adenovirus, according to a report published in Morbidity and Mortality Weekly Report.
“This cluster, along with recently identified possible cases in Europe, suggests that adenovirus should be considered in the differential diagnosis of acute hepatitis of unknown etiology among children,” Julia M. Baker, PhD, an epidemic intelligence service officer at the CDC National Center for Immunization and Respiratory Diseases, and colleagues, wrote. “Clinicians and laboratorians should be aware of possible differences in adenovirus test sensitivity for different specimen types; tests using whole blood might be more sensitive than those using plasma.
“CDC is monitoring the situation closely to understand the possible cause of illness and identify potential efforts to prevent or mitigate illness. Enhanced surveillance is underway in coordination with jurisdictional public health partners.”
From October to November 2021, five pediatric patients with severe hepatitis and adenovirus infection were identified at Children’s of Alabama hospital, prompting an investigation by hospital clinicians, state and county health departments and the CDC.
Baker and colleagues reviewed hospital records to identify patients with hepatitis and adenovirus infection, as diagnosed by PCR testing, seen on or after October 1, 2021. Four additional children were identified between October 2021 and February 2022, bringing the total to nine (median age, 2 years, 11 months; seven female patients). All children were immunocompetent with no clinically significant medical comorbidities. No additional patients were identified after a February 2022 stateside health advisory was issued.
Investigators noted that prior to admission, seven patients reported vomiting, six reported diarrhea and three reported upper respiratory symptoms. At admission, eight patients had scleral icterus, seven had hepatomegaly, six had jaundice and one had encephalopathy. All patients had elevated transaminases, and total bilirubin ranged from normal to elevated (range = 0.23-13.5 mg/dL, elevated in eight patients). All patients tested negative for hepatitis viruses A, B and C and several other causes of pediatric hepatitis and infections, including autoimmune hepatitis, Wilson disease, bacteremia, urinary tract infections and SARS-CoV-2 infection.
According to investigators, real-time PCR detected adenovirus in whole blood specimens from all patients, and hexon gene hypervariable region sequencing identified adenovirus type 41 in five patients. In addition, seven patients were coinfected with other viral pathogens, including enterovirus/rhinovirus, metapneumovirus, respiratory syncytial virus and human coronavirus OC43. Six patients received positive test results for Epstein-Barr virus (EBV) via PCR testing; however, those patients tested negative for EBV immunoglobulin M antibodies, which suggests possible low-level reactivation of previous infection, rather than acute infection.
Six patients underwent liver biopsies, which revealed varying degrees of hepatitis with no viral inclusion or immunohistochemical evidence of adenovirus. Acute liver failure developed in three patients, two of whom were treated with off-label cidofovir and steroids and later underwent liver transplantation. Both patients initially tested negative for adenovirus by real-time PCR on plasma specimens but later tested positive with whole blood specimens.
All patients, including the two LT recipients, have recovered or are recovering.
“Clinicians are encouraged to report possible cases of pediatric hepatitis with unknown etiology occurring on or after October 1, 2021, to public health authorities for further investigation,” the authors concluded.